ChiCTR2300071483 版本V1.1 版本创建时间2023/06/09 16:55:31 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

ChiCTR2300071483 

最近更新日期：

Date of Last Refreshed on：

2023-05-16 16:03:59 

注册时间：

Date of Registration：

2023-05-16 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

评估氨酚羟考酮缓释片与氨酚羟考酮片在健康志愿者中的单中心、随机、两周期、交叉比较药代动力学研究

Public title：

Evaluation of a single-center, randomized, two-cycle, crossover comparative pharmacokinetic study of aminophenoxycodone extended-release tablets versus aminophenoxycodone tablets in healthy volunteers

注册题目简写：

English Acronym：

研究课题的正式科学名称：

评估氨酚羟考酮缓释片与氨酚羟考酮片在健康志愿者中的单中心、随机、两周期、交叉比较药代动力学研究

Scientific title：

Evaluation of a single-center, randomized, two-cycle, crossover comparative pharmacokinetic study of aminophenoxycodone extended-release tablets versus aminophenoxycodone tablets in healthy volunteers

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

张美琳 

研究负责人：

阳国平 

Applicant：

Meilin Zhang 

Study leader：

Guoping Yang 

申请注册联系人电话：

Applicant telephone：

+86 193 0741 2080

研究负责人电话：

Study leader's telephone：

+86 731 8991 8665

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

zhangmeilin69@163.com

研究负责人电子邮件：

Study leader's E-mail：

ygp9880@126.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

湖南省长沙市岳麓区桐梓坡路138号

研究负责人通讯地址：

湖南省长沙市岳麓区桐梓坡路138号

Applicant address：

No. 138, Tongzipo Road, Yuelu District, Changsha City, Hunan Province

Study leader's address：

No. 138, Tongzipo Road, Yuelu District, Changsha City, Hunan Province

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

中南大学湘雅三医院临床试验中心

Applicant's institution：

Clinical Trial Center of the Third Xiangya Hospital of Central South University

研究负责人所在单位：

中南大学湘雅三医院临床试验中心

Affiliation of the Leader：

Clinical Trial Center of the Third Xiangya Hospital of Central South University

是否获伦理委员会批准：

是/Yes

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

23049

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

中南大学湘雅三医院伦理委员会

Name of the ethic committee：

IRB,theThird Xiangya Hospital of Central South University

伦理委员会批准日期：

Date of approved by ethic committee：

2023-03-23 00:00:00

伦理委员会联系人：

王晓敏

Contact Name of the ethic committee：

Xiaomin Wang

伦理委员会联系地址：

湖南省长沙市岳麓区桐梓坡路138号中南大学湘雅三医院伦理委员会

Contact Address of the ethic committee：

IRB,theThird Xiangya Hospital of Central South University,138Tongzipo Road,Yuelu District,Changsha,Hunan,China

伦理委员会联系人电话：

Contact phone of the ethic committee：

+86 731 8861 8938

伦理委员会联系人邮箱：

Contact email of the ethic committee：

研究实施负责（组长）单位：

中南大学湘雅三医院临床试验中心

Primary sponsor：

Clinical Trial Center of Third Xiangya Hospital of Central South University

研究实施负责（组长）单位地址：

湖南省长沙市岳麓区桐梓坡路138号

Primary sponsor's address：

138Tongzipo Road,Yuelu District,Changsha,Hunan,China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

湖南

市(区县)：

长沙

Country：

China

Province：

Hunan

City：

Changsha

单位(医院)：

中南大学湘雅三医院

具体地址：

湖南省长沙市岳麓区桐梓坡路138号

Institution
hospital：

Third Xiangya Hospital, Central South University

Address：

138Tongzipo Road,Yuelu District,Changsha,Hunan,China

经费或物资来源：

宜昌人福药业有限责任公司

Source(s) of funding：

Yichang Renfu Pharmaceutical Co.

Target disease：

Chronic pain

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 I期临床试验 

Study phase：

1

研究设计：

随机交叉对照 

Study design：

Cross-over 

研究目的：

1）单次使用氨酚羟考酮缓释片的药代动力学特征； 2）比较氨酚羟考酮缓释片与氨酚羟考酮片的药代动力学特征； 3）单次使用氨酚羟考酮缓释片的安全性；  

Objectives of Study：

1) Pharmacokinetic characteristics of a single dose of aminophenoxycodone extended-release tablets; 2) Comparison of the pharmacokinetic characteristics of aminophenoxycodone extended-release tablets with those of aminophenoxycodone tablets; (3) Safety of a single dose of aminophenoxycodone extended-release tablets;

药物成份或治疗方案详述：

氨酚羟考酮片是含有中枢神经镇痛作用的盐酸羟考酮和周围神经镇痛作用的对乙酰氨基酚组成的复方片剂。通过协同作用提高镇痛强度，同时可在低于单方药物处方量的剂量下减少盐酸羟考酮用量，具有“阿片节约效应”，降低副作用，同时减少了非甾体抗炎药对乙酰氨基酚的胃肠道刺激作用，降低了羟考酮的成瘾性且镇痛时间长、效果强、使用安全、扬长避短地发挥两种药物成分的最佳性能。 这是一项开放、单中心、随机、两周期、两序列、交叉比较药代动力学研究。计划入组24例志愿者，男女均有，随机分为A组和B组，每组12例。试验用药品每周期给药1-2次，清洗期7天，采用高效液相色谱-串联质谱法测定不同采样时间血浆中羟考酮和对乙酰氨基酚的血药浓度。采用非房室模型求算药动学参数，并进行统计分析。 

Description for medicine or protocol of treatment in detail：

Oxycodone tablets are a combination tablet containing oxycodone hydrochloride for central nerve analgesia and acetaminophen for peripheral nerve analgesia. It can improve the analgesic strength through synergistic effect, and at the same time reduce the dosage of oxycodone hydrochloride at a dose lower than the prescription amount of the single drug, which has "opioid saving effect" and reduces the side effects, and at the same time reduces the gastrointestinal irritation of acetaminophen, which is a non-steroidal anti-inflammatory drug, and reduces the addiction of oxycodone. The study was conducted in an open, single-center, randomized study to determine the optimal performance of the two drug components. This is an open, single-center, randomized, two-cycle, two-sequence, cross-comparative pharmacokinetic study. Twenty-four volunteers, both male and female, were randomized into groups A and B. Twelve volunteers were enrolled in each group. The experimental drugs were administered 1-2 times per cycle with a 7-day washout period, and the blood concentrations of oxycodone and acetaminophen in plasma at different sampling times were determined by high performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were calculated using a non-atrial chamber model and statistical analysis was performed. 

纳入标准：

志愿者必须符合下列所有标准才能入选： 1) 志愿者充分了解试验目的、性质、方法以及可能发生的不良反应，自愿作为志愿者，并在任何研究程序开始前签署知情同意书； 2) 志愿者能够和研究者进行良好的沟通，并且理解和遵守本项研究的各项要求； 3) 志愿者（包括男性志愿者）在试验前14天内已采取有效的避孕措施且愿意在试验期间及末次给药后6个月内无妊娠计划且自愿采取有效避孕措施； 4) 年龄为18～65周岁男性和女性志愿者（包括临界值）； 5) 男性志愿者体重不低于50公斤。女性志愿者体重不低于45公斤。体重指数（BMI）＝体重（kg）/身高2（m2），体重指数在19.0~26.0范围内（包括临界值）；

Inclusion criteria

To be enrolled, volunteers must meet all of the following criteria: 1) The volunteer fully understands the purpose, nature, methods, and possible adverse effects of the trial, volunteers voluntarily as a volunteer, and signs an informed consent form prior to the start of any study procedures; 2) The volunteer is able to communicate well with the investigator and understands and complies with the requirements of the study; 3) Volunteers (including male volunteers) are using effective contraception within 14 days prior to the trial and are willing to have no pregnancy plans and voluntarily use effective contraception during the trial and for 6 months after the last dose; 4) Male and female volunteers aged 18 to 65 years (including the threshold); 5) Male volunteers weighing no less than 50 kg. Female volunteers weighing no less than 45 kg. Body mass index (BMI) = weight (kg)/height2 (m2), with BMI in the range of 19.0 to 26.0 (including critical values);

排除标准：

符合一条或多条下列标准的志愿者将被排除： 1) 既往或目前正患有循环系统、内分泌系统、神经系统、消化系统、呼吸系统、泌尿生殖系统、血液学、免疫学、精神病学及代谢异常等任何临床严重疾病者或能干扰试验结果的任何其他疾病； 2) 有精神疾病（例如严重抑郁症）个人史或家族史； 3) 有药物、食物或其他物质过敏史； 4) 试验前4周内接受过外科手术，或计划在研究期间进行外科手术者； 5) 试验前14天内服用过任何药物或保健品者（包括中草药）； 6) 试验前30天内使用过任何抑制或诱导肝脏对药物代谢的药物（如：诱导剂—巴比妥类、卡马西平、苯妥英、糖皮质激素、奥美拉唑；抑制剂—SSRI类抗抑郁药、西咪替丁、地尔硫卓、大环内酯类、硝基咪唑类、镇静催眠药、维拉帕米、氟喹诺酮类、抗组胺类）者； 7) 试验前3个月内参加任何临床试验且服用了任何临床试验药物者； 8) 在入选前3个月内献血或大量失血（≥200 mL，不包括女性月经期失血）、接受输血或使用血制品者； 9) 妊娠或哺乳期妇女，以及志愿者试验期间不能采用一种或一种以上的非药物避孕措施者； 10) 对饮食有特殊要求，不能遵守统一饮食者； 11) 每天饮用过量茶、咖啡和/或含咖啡因的饮料（8杯以上，1杯=250 mL）者； 12) 嗜烟者或试验前3个月每日吸烟量多于5支者或试验期间不能停止使用任何烟草类产品者； 13) 酗酒者（包括酒精的滥用或成瘾）或试验前6个月内经常饮酒者，即每周饮酒超过14单位酒精（1单位=360 mL啤酒或45 mL酒精量为40%的烈酒或150 mL葡萄酒）或试验期间不能停止使用任何含酒精产品者； 14) 药物滥用者（包括药物的滥用或成瘾）或试验前3个月使用过软毒品（如：大麻）或试验前1年服用硬毒品（如：可卡因、苯环己哌啶等）者； 15) 生命体征异常者（收缩压<90 mmHg或>140 mmHg，舒张压<50 mmHg或>90 mmHg；心率<50 bpm或>100 bpm）或体格检查、心电图、实验室检查异常有临床意义（以临床研究医生判断为准）； 16) 有体位性低血压、晕针或晕血史或静脉穿刺采血不耐受者； 17) 试验前1个月内接种过疫苗或计划在试验期间接种疫苗者； 18) 志愿者可能因为其他原因而不能完成本研究或研究者认为不应纳入者。

Exclusion criteria：

Volunteers who meet one or more of the following criteria will be excluded: 1) Persons with any previous or current clinically serious disease of the circulatory, endocrine, neurological, digestive, respiratory, genitourinary, hematological, immunological, psychiatric and metabolic abnormalities or any other disease that can interfere with the results of the test; 2) A personal history or family history of a psychiatric disorder (e.g., major depressive disorder) 3) A history of allergy to drugs, food or other substances 4) have undergone surgical procedures within 4 weeks prior to the trial or are scheduled to have surgical procedures during the study 5) those who have taken any medication or supplements (including herbal remedies) within 14 days prior to the trial 6) Any drug that inhibits or induces hepatic metabolism of drugs within 30 days prior to the trial (e.g., inducers - barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; inhibitors - SSRI antidepressants, cimetidine, diltiazem, macrolides, nitroimidazoles, sedative-hypnotics, verapamil (Pami, fluoroquinolones, antihistamines); 7) Those who participated in any clinical trial and took any clinical trial drug within the 3 months prior to the trial 8) those who have donated blood or lost a significant amount of blood (≥200 mL, excluding blood loss during menstruation in women), received a blood transfusion or used blood products within 3 months prior to enrollment 9) Pregnant or lactating women, and those who cannot use one or more non-pharmaceutical contraceptive measures during the volunteer trial 10) Those who have special dietary requirements and cannot comply with a uniform diet 11) Those who consume excessive amounts of tea, coffee and/or caffeinated beverages (more than 8 cups, 1 cup = 250 mL) per day 12) smokers or those who smoked more than 5 cigarettes per day in the 3 months prior to the trial or those who could not stop using any tobacco-based products during the trial 13) alcoholics (including alcohol abuse or addiction) or regular drinkers in the 6 months prior to the trial, i.e., those who consume more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of 40% alcohol spirits or 150 mL of wine) or those who are unable to stop using any alcohol-containing products during the trial 14) Substance abusers (including drug abuse or addiction) or those who have used soft drugs (e.g., marijuana) in the 3 months prior to the trial or hard drugs (e.g., cocaine, phencyclidine, etc.) in the 1 year prior to the trial 15) Those with abnormal vital signs (systolic blood pressure <90 mmHg or >140 mmHg, diastolic blood pressure <50 mmHg or >90 mmHg; heart rate <50 bpm or >100 bpm) or abnormal physical examination, electrocardiogram, or laboratory tests of clinical significance (as judged by the clinical study physician); 16) Those with a history of postural hypotension, needle or blood sickness or intolerance to venipuncture blood collection; 17) Those who have received vaccines within 1 month prior to the trial or who plan to receive vaccines during the trial 18) Volunteers who may not be able to complete the study for other reasons or who, in the opinion of the investigator, should not be included.

研究实施时间：

Study execute time：

从 From 2023-05-17 00:00:00至 To 2026-05-17 00:00:00  

征募观察对象时间：

Recruiting time：

从From 2023-05-17 00:00:00 至 To 2026-05-17 00:00:00  

干预措施：

Interventions：

组别：

A组

样本量：

12

Group：

Group A

Sample size：

干预措施：

计划入组24例志愿者，男女均有，随机分为A组和B组，每组12例。两个给药周期，两种给药方案（T1和T2）。第一周期：志愿者按照1:1的比例随机分配至2个给药组（A组和B组）之一，于给药前1天晚餐前入住Ⅰ期病房，入住研究中心后统一进食标准晚餐。所有志愿者空腹至少10小时后，在早上开始服药，志愿者在空腹状态下用240mL温水送服相应试验用药品。A组志愿者按给药方案一（T1）给药：于给药当天早晨空腹口服氨酚羟考酮缓释片5mg/325mg(盐酸羟考酮/对乙酰氨基酚)2片。清洗期7天，第二周期：志愿者均按相应的给药序列分别给予另一种给药方案，重复第一周期程序，并进行安全性检查后出组。

干预措施代码：

Intervention：

Twenty-four volunteers, both male and female, were planned to be enrolled and randomized into groups A and B, with 12 cases in each group. Two dosing cycles with two dosing regimens (T1 and T2). Cycle 1: Volunteers were randomly assigned to one of the 2 dosing groups (Group A and Group B) in a 1:1 ratio, admitted to the Phase I ward before dinner 1 day prior to dosing, and fed a standard dinner uniformly after admission to the study center. After fasting for at least 10 hours, all volunteers started taking the drug in the morning. volunteers were given the corresponding experimental drug with 240 mL of warm water in the fasting state. volunteers in group A were administered according to dosing regimen I (T1): 2 tablets of aminophenol oxycodone extended-release tablets 5 mg/325 mg (oxycodone hydrochloride/acetaminophen) were given orally in the morning of the dosing day on an empty stomach. The washout period was 7 days, and in the second cycle: volunteers were all given another dosing regimen according to the corresponding dosing sequence, respectively, and the first cycle procedure was repeated, and the group was discharged after a safety check.

Intervention code：

组别：

B组

样本量：

12

Group：

Group B

Sample size：

干预措施：

计划入组24例志愿者，男女均有，随机分为A组和B组，每组12例。两个给药周期，两种给药方案（T1和T2）。第一周期：志愿者按照1:1的比例随机分配至2个给药组（A组和B组）之一，于给药前1天晚餐前入住Ⅰ期病房，入住研究中心后统一进食标准晚餐。所有志愿者空腹至少10小时后，在早上开始服药，志愿者在空腹状态下用240mL温水送服相应试验用药品。B组志愿者按给药方案二（T2）给药：于给药当天早晨空腹口服1片氨酚羟考酮片5mg/325mg(盐酸羟考酮/对乙酰氨基酚)，并于当天第一次给药后6h口服1片氨酚羟考酮片5mg/325mg(盐酸羟考酮/对乙酰氨基酚)。清洗期7天，第二周期：志愿者均按相应的给药序列分别给予另一种给药方案，重复第一周期程序，并进行安全性检查后出组。

干预措施代码：

Intervention：

Twenty-four volunteers, both male and female, were planned to be enrolled and randomized into groups A and B, with 12 cases in each group. Two dosing cycles with two dosing regimens (T1 and T2). Cycle 1: Volunteers were randomly assigned to one of the 2 dosing groups (Group A and Group B) in a 1:1 ratio and admitted to the Phase I ward before dinner 1 day prior to dosing, and a standard dinner was consumed uniformly after admission to the study center. All volunteers started taking the drug in the morning after fasting for at least 10 hours, and the volunteers were given the appropriate test drug with 240 mL of warm water on an empty stomach. Oxycodone tablets 5mg/325mg (oxycodone hydrochloride/acetaminophen) were administered orally 6h after the first dose on the same day. The washout period was 7 days and the second cycle: volunteers were all given another dosing regimen in the corresponding dosing sequence, respectively, and the first cycle procedure was repeated, and safety checks were performed before leaving the group.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 湖南 

市(区县)：

 长沙 

Country：

China 

Province：

Hunan 

City：

Changsha 

单位(医院)：

中南大学湘雅三医院 

单位级别：

三甲 

Institution
hospital：

Third Xiangya Hospital, Central South University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

PK指标

指标类型：

主要指标

Outcome：

PK Indicators

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

不良事件（AE）

指标类型：

主要指标

Outcome：

adverse events

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

实验室检查

指标类型：

主要指标

Outcome：

laboratory test

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

体格检查

指标类型：

主要指标

Outcome：

Physical examination

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

生命体征

指标类型：

主要指标

Outcome：

vital signs

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

12导联心电图

指标类型：

主要指标

Outcome：

Twelve-lead electrocardiogram

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

Sample Name：

blood

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

标本中文名：

尿液

组织：

Sample Name：

Urine

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 岁 years
最大 Max age 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

随机表由统计单位采用SAS（9.4或更高版本）产生，随机时志愿者将按照筛选号从小到大获得随机号。 采用区组随机化方法，组间比例为1:1，生成随机号及其对应的组别（A组和B组）。随机号为：K001 ~K024。

Randomization Procedure (please state who generates the random number sequence and by what method)：

The randomization table was generated by the statistical unit using SAS (version 9.4 or higher), and at randomization volunteers will receive random numbers according to the screening number from smallest to largest. The randomization method of zone group randomization with a 1:1 ratio between groups was used to generate the random numbers and their corresponding groups (Group A and Group B). The randomization numbers are: K001 ~ K024.

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

本次临床研究为开放性研究，除生物样本检测人员外，对其他临床试验人员不设盲。在数据统计分析前，生物样本检测分析人员将不获得志愿者分组信息及随机给药信息，以消除样本测试过程中可能存在的偏移。

Blinding：

This clinical study is an open study and will not be blinded to clinical trial personnel other than the biospecimen testing personnel. Prior to statistical analysis of the data, the biospecimen testing analysts will not be provided with volunteer grouping information and random drug administration information in order to eliminate possible bias during sample testing.

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

否

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

no

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

数据管理计划（DMP）：DMP作为数据管理的指导性文件由数据管理员（DM）撰写，申办方批准，数据管理工作将根据DMP定义的时间、内容及方法进行。 电子病例报告表（eCRF）：数据管理员根据试验方案设计构建，并根据逻辑核查计划（DVP）设置逻辑核查，通过测试并获申办方批准后发布使用。

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

Data Management Plan (DMP): The DMP serves as the guiding document for data management written by the Data Manager (DM) and approved by the sponsor. Data management will be carried out according to the time, content and methods defined in the DMP. Electronic Case Report Form (eCRF): designed and constructed by the Data Manager in accordance with the trial protocol and set up for logical verification in accordance with the Logical Verification Plan (DVP), tested and approved by the sponsor before being released for use.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

暂未确定/Not yet

注册人：

Name of Registration：

  2023-05-16 16:03:53